An update on heart disease risk associated with testosterone boosting medications

Introduction: The cardiovascular (CV) safety of testosterone replacement therapy (TRT) remains a crucial issue in the management of subjects with late-onset hypogonadism. The authors systematically reviewed and discussed the available evidence focusing our analysis on heart-related issues.

Areas covered: All the available data from prospective observational studies evaluating the role endogenous T levels on the risk of acute myocardial infarction (AMI) were collected and analyzed. In addition, the impact of TRT on heart-related diseases, as derived from pharmaco-epidemiological studies as well as from randomized placebo-controlled trials (RCTs), was also investigated.

Expert opinion: Available evidence indicates that endogenous low T represents a risk factor of AMI incidence and its related mortality. TRT in hypogonadal patients is able to improve angina symptoms in subjects with ischemic heart diseases and exercise ability in patients with heart failure (HF). In addition, when prescribed according to the recommended dosage, TRT does not increase the risk of heart-related events.     

Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV-1

IntroductionErectile dysfunction (ED) is associated with neurological damage due to human T-lymphotropic virus 1 (HTLV-1) infection, but hormonal and psychogenic factors also cause ED.AimTo evaluate the association of psychogenic and hormonal factors with ED in men infected with HTLV-1.MethodsIn this cross-sectional study, we compared total testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, anxiety symptoms, depressive symptoms, and neurologic manifestations in HTLV-1-infected men with or without ED. The International Index of Erectile Function was used to determine the degree of ED. Participants were grouped according to Osame’s Motor Disability Scale and the Expanded Disability Status Scale: HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), probable HAM/TSP, or HTLV-1 carrier. Chi-square and Fisher’s exact tests were used to compare the groups, and regression analyses were used to show predictors of ED.Main Outcome MeasureSexual hormonal levels, psychogenic factors, and neurologic disabilities were found to be associated with ED.ResultsED was associated with age older than 60 years (P < .001), degree of neurologic involvement (P < .001), depression (P = .009), and anxiety (P = .008). In the multivariate analyses, only age and degree of neurological injury remained as risk factors for ED.Clinical ImplicationsNeurological manifestations are a stronger predictor of ED than hormonal and psychogenic factors in HTLV-1-infected men.Strengths & LimitationsThe statistical power of the study was limited due to the low number of participants, but neurologic manifestations were clearly associated with ED. There was no strong association between hormonal and psychogenic factors and ED.ConclusionHormonal and psychogenic factors did not show a strong association with ED in individuals with HTLV-1, but neurological manifestations were strongly associated with ED in these individuals.de Oliveira CJV, Neto, JAC, Andrade RCP, et al. Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV–1. J Sex Med 2019; 16:1763–1768.     

An association between diet,metabolic syndrome and lower urinary tract symptoms

Diet is a key factor in the aetiology of many diseases, including metabolic syndrome and lower urinary tract disorders. Metabolic syndrome is a growing and increasingly expensive health problem in both the developed and the developing world, with an associated rise in morbidity and mortality. On the other hand, lower urinary tract symptoms affect millions of individuals worldwide, lowering their quality of life. Associations have been established between both conditions in existing literature and the various components of the metabolic syndrome have been linked with the onset and aggravation of symptoms in various forms of LUTS. This current review explores the relationships between these in detail, focusing on their inter-relationships particularly vis-a-vis dietary macronutrient and micronutrient intake.     

Tribulus terrestris versus placebo en el tratamiento de la disfunción eréctil: un estudio aleatorizado,prospectivo y doble ciego

ObjectivesTo evaluate the possible effects of Tribulus terrestris herbal medicine in the erectile dysfunction treatment and to quantify its potential impact on serum testosterone levels.Design and methodsProspective, randomized, double-blind and placebo-controlled study including thirty healthy men selected from 100 patients who presented themselves spontaneously complaining of erectile dysfunction, ≥ 40 years of age, nonsmokers, not undergoing treatment for prostate cancer or erectile dysfunction, no dyslipidemia, no phosphodiesterase inhibitor use, no hormonal manipulation and, if present hypertension and/or diabetes mellitus should be controlled. International Index of Erectile Function (IIEF-5) and serum testosterone were obtained before randomization and after 30 days of study. Patients were randomized into two groups of fifteen subjects each. The study group received 800 mg of Tribulus terrestris, divided into two doses per day for thirty days and the control group received placebo administered in the same way.ResultsThe groups were statistically equivalent in all aspects evaluated. The mean (SD) age was 60 (9.4) and 62.9 (7.9), P = .36 for intervention and placebo groups, respectively. Before treatment, the intervention group showed mean IIEF-5 of 13.2 (5-21) and mean total testosterone 417.1 ng/dl (270.7-548.4 ng/dl); the placebo group showed mean IIEF-5 of 11.6 (6-21) and mean total testosterone 442.7 ng/dl (301-609.1 ng/dl). After treatment, the intervention group showed mean IIEF-5 of 15.3 (5-21) and mean total testosterone 409.3 ng/dl (216.9-760.8 ng/dl); the placebo group showed mean IIEF-5 of 13.7 (6-21) and mean total testosterone 466.3 ng/dl (264.3-934.3 ng/dl). The time factor caused statistically significant changes in both groups for IIEF-5 only (P = .0004), however, there was no difference between the two groups (P = .7914).ConclusionsAt the dose and interval studied, Tribulus terrestris was not more effective than placebo on improving symptoms of erectile dysfunction or serum total testosterone.     

Regulation of male fertility by the bone-derived hormone osteocalcin

Traditionally, bone has been viewed as a relatively static tissue only fulfilling mechanical and scaffolding function. In the past decade however, this classical view of the bone has considerably evolved towards a more complex picture. It is now clear that the skeleton is not only a recipient for hormonal input but it is also an endocrine organ itself. Through the secretion of an osteoblast-derived molecule, osteocalcin, the skeleton regulates glucose homeostasis and male reproductive functions. When undercarboxylated, osteocalcin acts following its binding to a G-coupled receptor, Gprc6a, on pancreatic β cells to increase insulin secretion, on muscle and white adipose tissue to promote glucose homeostasis and on Leydig cells of the testis to favor testosterone biosynthesis. More recently, it was also shown that osteocalcin acts via a pancreas-bone-testis axis that regulates, independently of and in parallel to the hypothalamus–pituitary–testis axis, male reproductive functions by promoting testosterone biosynthesis. Lastly, in trying to expand the biological relevance of osteocalcin from mouse to human, it was shown that Gprc6a is a potential new susceptibility locus for primary testicular failure in humans. Altogether, these results shed new light on the importance of the endocrine role of the skeleton and also provide credence to the search for additional endocrine functions of this organ.     

Antireproductive effect of calcium channel blockers on male rats

Introduction  Drugs have been shown to adversely affect male fertility and recently anti-hypertensive drugs were added to the list. The anti-fertility effects of nifedipine and similar calcium channel blockers are well-illustrated in in vitro experiments but not in vivo. Purpose  The present study was designed to experimentally elucidate the sub-chronic effect of nifedipine, verapamil and diltiazem on sperm functions and reproductive hormone levels in vivo. Methods  Male rats (150–200 g) were divided into four groups of ten rats each. Group 1 (control) received distilled water; Group 2 received nifedipine 0.57 mg/kg BW; Group 3 were given verapamil 3.40 mg/kg BW and Group 4 were given diltiazem 2.57 mg/kg BW. Each drug-treated group had its own recovery group from which treatment was discontinued for 30 days before the animals were sacrificed. Blood samples were collected for hormonal assay of FSH, LH and testosterone. Semen evaluation was done and the testes, seminal vesicle, epididymis and prostate were removed, and weighed immediately. Results  Nifedipine, verapamil and diltiazem significantly decreased (P < 0.05) sperm count and motility in drug treated groups. The weight of the epididymis was significantly reduced (P < 0.05) in the drug treated rats. Semen parameters and other associated changes were restored after 30 days of drug withdrawal. Conclusion  Calcium channel blockers appear to have a reversible anti-fertility effect on male rats which does not occur through inhibition of the pituitary-gonadal axis.     

十一酸睾酮对雄性家兔髂动脉内膜损伤后的修复作用

目的观察十一酸睾酮对雄兔髂动脉内膜损伤后的修复作用。方法成熟雄性日本大耳白兔25只,随机分成5组,每组5只:假手术组(不切除睾丸和附睾)、模型组、小剂量组(手术后补充睾酮3mg/kg)、中剂量组(手术后补充睾酮6mg/kg)和大剂量组(手术后补充睾酮12mg/kg),后4组均切除双侧睾丸和附睾。所有动物手术后第14d行右侧髂动脉内皮剥脱术。手术后第7、14和第21d肌肉注射十一酸睾酮,假手术组和模型组肌注生理盐水。于不同时间测定血清总睾酮。第28d处死动物,取损伤血管段,应用扫描电镜和HE染色观察髂动脉内膜的修复情况。结果光镜下观察发现,模型组、小剂量组和中剂量组动脉内膜增生严重,大剂量组内膜增厚程度明显减低,接近假手术组。模型组、小剂量组和中剂量组的髂动脉内膜/中膜面积比值分别是1.25±0.10、0.90±0.10和0.74±0.11,明显高于假手术组(0.22±0.05;P<0.01)。大剂量组的髂动脉内膜/中膜面积比值为0.26±0.07,接近于假手术组(P>0.05)。扫描电镜观察发现,假手术组动物髂动脉内皮光滑,整齐连续,模型组几乎未见到有内皮细胞再生,小剂量组内皮有散在覆盖,中剂量组片状覆盖,大剂量组内皮细胞修复明显,排列趋于正常,偶有缺失。在手术后第28d大剂量组血清总睾酮水平接近假手术组,其它组在不同时间点均低于假手术组。结论生理水平的睾酮具有保护雄性家兔血管内皮,抑制动脉损伤后内膜增生的作用。